Decitabine

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and AbbVie announced today the outcome from the Phase III VERONA study (NCT04401748) investigating Venclexta® (venetoclax) plus azacitidine for patients with previously untreated higher-risk myelodysplastic syndromes (MDS). The study did not meet the primary endpoint of overall survival at the final analysis. The safety profile of the Venclexta combination was consistent with the known risk of the individual study medicines and no unexpected safety signals were observed. Full data will be presented at an upcoming medical meeting in 2025. VERONA is a global, AbbVie-led, Phase III, multicenter, randomized, double-blind study evaluating Venclexta in combination with azacitidine compared to placebo plus azacitidine in treatment-naïve patients with higher-risk MDS. The study includes approximately 500 patients across 220 sites globally who were randomly assigned to either Venclexta plus azacitidine or placebo plus azacitidine. Patients who received Venclexta in combination with azacitidine through participation in the MDS clinical trials will be informed by their treating physician. The results of the VERONA study have no impact on the approved indications for Venclexta or any ongoing studies. About Venclexta® (venetoclax) Venclexta is a first-in-class targeted medicine designed to bind selectively and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to help restore the process of apoptosis. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood cancers. Venclexta® (venetoclax) U.S. Indication Venclexta is a prescription medicine used: to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who: are 75 years of age or older, or have other medical conditions that prevent the use of standard chemotherapy. are 75 years of age or older, or have other medical conditions that prevent the use of standard chemotherapy. It is not known if Venclexta is safe and effective in children. Important Safety Information What is the most important information patients should know about Venclexta? Venclexta can cause serious side effects, including: Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein. The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS. Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased. The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose. What patients should not take Venclexta? Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS. Patients should tell their doctor about all the medicines they take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects. Patients must not start new medicines during treatment with Venclexta without first talking with their doctor. Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they: Have kidney or liver problems. Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium. Have a history of high uric acid levels in the blood or gout. Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta. Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away. Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose. What to avoid while taking Venclexta: Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood. What are the possible side effects of Venclexta? Venclexta can cause serious side effects, including: Low white blood cell counts (neutropenia) . Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing. Infections . Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta. The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet. The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure. Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility. These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555. Please see the Venclexta full Prescribing Information, including the Medication Guide, for additional Important Safety Information. About Genentech in Hematology For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

– 26% (20/77) CR+CRh rate and 48% (37/77) ORR in efficacy-evaluable pivotal R/R mNPM1 AML population – – Robust responses observed across subgroups, regardless of co-mutations, number of prior lines of therapy, or prior venetoclax, within efficacy-evaluable pivotal R/R mNPM1 AML population – – 60% (3/5) ORR in Ph 1 patients with R/R NUP98r AML – June 12, 2025 -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today announced new data from the pivotal AUGMENT-101 trial of Revuforj® (revumenib), the Company’s first-in-class menin inhibitor, in patients with relapsed or refractory (R/R) mutant NPM1 (mNPM1) and NUP98-rearranged (NUP98r) acute myeloid leukemia (AML). The data are being presented in posters at the 30th European Hematology Association (EHA) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually. “The new data from AUGMENT-101 continue to highlight Revuforj’s best-in-class profile and its potential to transform the treatment paradigm for acute leukemia patients with certain genetic alterations,” said Nick Botwood, M.B.B.S., Head of Research & Development and Chief Medical Officer at Syndax. “The compelling AUGMENT-101 results led to the FDA approval of Revuforj for R/R acute leukemia with a KMT2A translocation and serve as the foundation for the supplemental NDA we submitted to the FDA for R/R mNPM1 AML, another area of high unmet need.” “Revumenib has shown a potential best-in-class efficacy profile and the latest data in R/R mNPM1 AML underscore the opportunity for revumenib to become a standard of care treatment for this patient population in addition to R/R KMT2Ar acute leukemia,” said Ibrahim Aldoss, M.D., Associate Professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope. “The revumenib data in R/R mNPM1 AML presented at EHA are impressive, with 26% of patients achieving CR/CRh and nearly 50% achieving an overall response with a medicine that was generally well-tolerated. Furthermore, the 23-month median overall survival observed in responders in a subgroup analysis is very encouraging.” The Phase 2 portion of the AUGMENT-101 trial of revumenib enrolled 84 patients with R/R mNPM1 AML. As previously reported, the primary endpoint was met in the protocol-defined primary analysis population which included the first 64 adults who met the efficacy evaluable criteria. At EHA 2025, the Company will highlight consistent results from all the efficacy-evaluable R/R mNPM1 AML patients (n=77) in the Phase 2 portion of AUGMENT-101 (DCO: September 2024). In this population, the median age was 63 (11-84), 20% had received four or more prior lines of therapy (median prior lines: 2), and 74% had previously received venetoclax. The complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate was 26% (20/77; 95% CI: 17%-37%). The median duration of CR/CRh response was 4.7 months (95% CI: 2.1-8.2) and the median time to first CR/CRh was 2.8 months (range: 0.9-8.8). Minimal residual disease (MRD) status was assessed in 19 of 20 patients who achieved CR/CRh, 63% (12/19) of whom were MRD negative. The overall response rate (ORR)1 was 48% (37/77; 95% CI: 37%-60%). Of the patients who achieved an overall response, five patients proceeded to hematopoietic stem cell transplant (HSCT) while in remission, with three patients resuming revumenib after HSCT. Four patients were in CR or CRh and one was in morphologic leukemia-free state (MLFS) when they proceeded to HSCT. Newly shared data from this single-arm trial show that the median overall survival (OS) observed was 4.8 months (95% CI: 3.4-8.4) among all efficacy-evaluable Phase 2 R/R mNPM1 AML patients, based on the Kaplan-Meier estimate. A new subpopulation analysis that will be reported at a future medical meeting show that a median OS of 23.3 months (95% CI: 8.4-NR) was observed among the 37 patients who achieved an overall response, based on the Kaplan-Meier estimate. Additionally, newly shared analyses from all efficacy-evaluable Phase 2 R/R mNPM1 AML patients show that CR+CRh responses were observed across subgroups, regardless of co-mutations, number of prior lines of therapy, or prior venetoclax exposure. The CR+CRh rate was 25%, 20%, and 33% among patients with one, two, or three or more prior lines of therapy, respectively. The CR+CRh rate was 45% (95% CI: 23%-69%) among patients without prior venetoclax exposure and 19% (95% CI: 10%-32%) among patients with prior venetoclax exposure. The AUGMENT-101 Phase 2 safety population included 84 adult and pediatric patients with R/R mNPM1 AML. Detailed results from this safety population were previously published in the journal Blood and will be summarized in the EHA presentation. The safety profile observed with revumenib in this population was consistent with previously reported data. Revumenib was generally well-tolerated with 4.8% (4/84) of patients discontinuing treatment due to treatment-related adverse events. The Phase 1 portion of the AUGMENT-101 trial of revumenib enrolled R/R acute leukemia patients with KMT2Ar, mNPM1, and other genetic alterations associated with upregulation of HOX, including five patients with NUP98-rearranged (NUP98r) AML. NUP98r is among a growing list of genetic abnormalities associated with upregulation of HOX in leukemia that are susceptible to menin inhibition in preclinical studies. Among the patients with R/R NUP98r AML, 60% (3/5) attained morphological remission, including one patient who proceeded to transplant, resumed revumenib post-transplant and was in maintenance cycle 10 as of the February 2024 data cutoff date. The safety profile of revumenib in patients with R/R NUP98r AML was consistent with previous reports observed in KMT2Ar or mNPM1 AML. To further explore the potential for menin inhibition in other genetic populations, a Phase 2 investigator-sponsored study evaluating revumenib in R/R acute leukemia associated with HOX upregulation, including patients with NUP98r AML, has been initiated (NCT06229912). Patients with NUP98r are also included in several other ongoing clinical trials of revumenib, such as the Phase 1 trial of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients and the Phase 1/2 SAVE trial of revumenib in combination with venetoclax and decitabine/cedazuridine in R/R and newly diagnosed patients with AML or mixed-lineage acute leukemia (MPAL). In the SAVE trial, a 100% (5/5) ORR was observed in patients with R/R NUP98r AML (DCO: November 2024). In addition to newly shared data from patients with R/R mNPM1 AML and NUP98r in the AUGMENT-101 trial, an encore presentation of data from patients with R/R KMT2Ar acute leukemia in the pivotal Phase 2 portion of the trial will also be presented. The data will be featured in a poster session titled “Updated Results and Longer Follow-Up From the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia.” Results from the pivotal AUGMENT-101 trial led to the FDA approval in November 2024 of Revuforj® (revumenib) for the treatment of R/R acute leukemia with a KMT2A translocation in adult and pediatric patients one year and older. Two other abstracts were accepted for publication-only. One is a ‘trial in progress’ abstract which describes the design of the ongoing Phase 1 study of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients with KMT2Ar, mNPM1, or NUP98r. The second abstract describes real-world treatment patterns in patients with R/R mNPM1 AML in the U.S. between January 2009 and June 2024. The posters and publication-only abstracts have been published on the virtual EHA congress platform. Copies of the posters will be made available in the ‘Publications & Meetings Presentations’ section of the Syndax website. Revuforj (revumenib) is an oral, first-in-class, selective menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older. Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Positive pivotal data from the AUGMENT-101 trial in this population with revumenib as a monotherapy were recently published and the Company submitted a supplemental NDA for revumenib in R/R mNPM1 AML in April 2025. Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing or planned across the treatment landscape, including in newly diagnosed patients. Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj® (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. References 1. Overall response rate (ORR) includes CR, CRh, CRp, CRi, MLFS, and PR; Composite complete remission (CRc) includes CR, CRh, CRp, and CRi. CR = Complete remission CRh = Complete remission with partial hematologic recovery CRp = Complete remission with incomplete platelet recovery CRi = Complete remission with incomplete count recovery MLFS = Morphologic leukemia-free state PR = Partial response The content above comes from the network. if any infringement, please contact us to modify.